IL207204A - Indole-3-ring carboxamides, process for making them, pharmacological compounds containing them and using them for the preparation of medicinal products - Google Patents

Info

Publication number

IL207204A

IL207204A IL207204A IL20720410A IL207204A IL 207204 A IL207204 A IL 207204A IL 207204 A IL207204 A IL 207204A IL 20720410 A IL20720410 A IL 20720410A IL 207204 A IL207204 A IL 207204A

Authority

IL

Israel

Prior art keywords

alkyl

phenyl

formula

compound

chosen

Prior art date

2008-01-31

Links

• Espacenet
• Global Dossier
• Discuss

• -1 Cyclic indole-3-carboxamides Chemical class 0.000 title claims description 254
• 238000000034 method Methods 0.000 title claims description 135
• 238000002360 preparation method Methods 0.000 title claims description 23
• 239000003814 drug Substances 0.000 title claims description 21
• 239000008194 pharmaceutical composition Substances 0.000 title claims description 13
• 230000008569 process Effects 0.000 title claims description 6
• 150000001875 compounds Chemical class 0.000 claims description 496
• 125000001424 substituent group Chemical group 0.000 claims description 130
• 239000000203 mixture Substances 0.000 claims description 103
• 150000003839 salts Chemical class 0.000 claims description 77
• 239000001257 hydrogen Substances 0.000 claims description 69
• 229910052739 hydrogen Inorganic materials 0.000 claims description 69
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 65
• 229910052736 halogen Inorganic materials 0.000 claims description 58
• 150000002367 halogens Chemical class 0.000 claims description 58
• 125000001072 heteroaryl group Chemical group 0.000 claims description 47
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 40
• 229910052731 fluorine Inorganic materials 0.000 claims description 38
• 239000011737 fluorine Substances 0.000 claims description 38
• 239000012453 solvate Substances 0.000 claims description 34
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 32
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 31
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 28
• 238000011282 treatment Methods 0.000 claims description 27
• 125000001153 fluoro group Chemical group F* 0.000 claims description 26
• 229910052757 nitrogen Inorganic materials 0.000 claims description 26
• 125000000217 alkyl group Chemical group 0.000 claims description 25
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 25
• 150000002431 hydrogen Chemical class 0.000 claims description 23
• 229910052799 carbon Inorganic materials 0.000 claims description 22
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
• 229910052760 oxygen Inorganic materials 0.000 claims description 15
• 239000002243 precursor Substances 0.000 claims description 14
• 125000000524 functional group Chemical group 0.000 claims description 13
• 125000006239 protecting group Chemical group 0.000 claims description 13
• 206010020772 Hypertension Diseases 0.000 claims description 12
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 12
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 11
• 206010019280 Heart failures Diseases 0.000 claims description 11
• 229910052717 sulfur Inorganic materials 0.000 claims description 11
• 125000001544 thienyl group Chemical group 0.000 claims description 10
• 229910052740 iodine Inorganic materials 0.000 claims description 8
• 208000017169 kidney disease Diseases 0.000 claims description 8
• 125000004076 pyridyl group Chemical group 0.000 claims description 8
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
• 208000001647 Renal Insufficiency Diseases 0.000 claims description 7
• 125000006709 (C5-C7) cycloalkenyl group Chemical group 0.000 claims description 6
• 208000035475 disorder Diseases 0.000 claims description 6
• 238000004519 manufacturing process Methods 0.000 claims description 6
• 206010049694 Left Ventricular Dysfunction Diseases 0.000 claims description 5
• 230000000747 cardiac effect Effects 0.000 claims description 5
• 208000037803 restenosis Diseases 0.000 claims description 5
• 208000010412 Glaucoma Diseases 0.000 claims description 4
• 206010061216 Infarction Diseases 0.000 claims description 4
• 230000006378 damage Effects 0.000 claims description 4
• 230000007574 infarction Effects 0.000 claims description 4
• 125000006531 (C2-C5) alkyl group Chemical group 0.000 claims description 3
• 206010002383 Angina Pectoris Diseases 0.000 claims description 3
• 206010007572 Cardiac hypertrophy Diseases 0.000 claims description 3
• 208000006029 Cardiomegaly Diseases 0.000 claims description 3
• 208000017442 Retinal disease Diseases 0.000 claims description 3
• 206010038923 Retinopathy Diseases 0.000 claims description 3
• 206010072810 Vascular wall hypertrophy Diseases 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 201000006370 kidney failure Diseases 0.000 claims description 3
• 201000002793 renal fibrosis Diseases 0.000 claims description 3
• 206010063897 Renal ischaemia Diseases 0.000 claims description 2
• 230000009787 cardiac fibrosis Effects 0.000 claims description 2
• 230000000302 ischemic effect Effects 0.000 claims description 2
• 230000000414 obstructive effect Effects 0.000 claims description 2
• 230000003836 peripheral circulation Effects 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 9
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 96
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 62
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 59
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 50
• 238000006243 chemical reaction Methods 0.000 description 47
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 42
• 239000000243 solution Substances 0.000 description 39
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
• 239000011541 reaction mixture Substances 0.000 description 35
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
• 229910052796 boron Inorganic materials 0.000 description 33
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 32
• 229910052938 sodium sulfate Inorganic materials 0.000 description 32
• 235000011152 sodium sulphate Nutrition 0.000 description 32
• 239000002904 solvent Substances 0.000 description 31
• 239000012044 organic layer Substances 0.000 description 30
• 238000005160 1H NMR spectroscopy Methods 0.000 description 27
• 125000004432 carbon atom Chemical group C* 0.000 description 26
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 25
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
• 108090000783 Renin Proteins 0.000 description 23
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
• 102100028255 Renin Human genes 0.000 description 21
• 230000015572 biosynthetic process Effects 0.000 description 21
• 239000003480 eluent Substances 0.000 description 21
• 238000002953 preparative HPLC Methods 0.000 description 21
• 238000010898 silica gel chromatography Methods 0.000 description 20
• 239000002253 acid Substances 0.000 description 19
• 230000002829 reductive effect Effects 0.000 description 19
• 239000007787 solid Substances 0.000 description 19
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 18
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
• 238000003786 synthesis reaction Methods 0.000 description 18
• 125000004433 nitrogen atom Chemical group N* 0.000 description 17
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
• 125000001041 indolyl group Chemical group 0.000 description 14
• 239000002585 base Substances 0.000 description 13
• 229910052801 chlorine Inorganic materials 0.000 description 13
• 238000001819 mass spectrum Methods 0.000 description 13
• 238000012360 testing method Methods 0.000 description 13
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 12
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• 150000001408 amides Chemical class 0.000 description 12
• 239000000460 chlorine Substances 0.000 description 12
• 201000010099 disease Diseases 0.000 description 12
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 11
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 11
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 11
• 229910052794 bromium Inorganic materials 0.000 description 11
• 230000005764 inhibitory process Effects 0.000 description 11
• 238000000752 ionisation method Methods 0.000 description 11
• 229910000027 potassium carbonate Inorganic materials 0.000 description 11
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 10
• 238000000132 electrospray ionisation Methods 0.000 description 10
• 229910052763 palladium Inorganic materials 0.000 description 10
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
• 230000000694 effects Effects 0.000 description 9
• 150000002475 indoles Chemical class 0.000 description 9
• 239000000543 intermediate Substances 0.000 description 9
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
• BKOOMYPCSUNDGP-UHFFFAOYSA-N 2-methylbut-2-ene Chemical compound CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 description 8
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 8
• 125000002843 carboxylic acid group Chemical group 0.000 description 8
• 238000001816 cooling Methods 0.000 description 8
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
• 239000007858 starting material Substances 0.000 description 8
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 7
• 239000004480 active ingredient Substances 0.000 description 7
• 239000000010 aprotic solvent Substances 0.000 description 7
• 239000012043 crude product Substances 0.000 description 7
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 7
• 230000003647 oxidation Effects 0.000 description 7
• 238000007254 oxidation reaction Methods 0.000 description 7
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
• FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 6
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
• 241001465754 Metazoa Species 0.000 description 6
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 6
• 125000003277 amino group Chemical group 0.000 description 6
• 239000003054 catalyst Substances 0.000 description 6
• 238000006555 catalytic reaction Methods 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 6
• 125000004122 cyclic group Chemical group 0.000 description 6
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 6
• 150000002148 esters Chemical class 0.000 description 6
• 150000002430 hydrocarbons Chemical group 0.000 description 6
• 239000003112 inhibitor Substances 0.000 description 6
• QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 6
• 230000000144 pharmacologic effect Effects 0.000 description 6
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 6
• UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 5
• FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 5
• 102400000345 Angiotensin-2 Human genes 0.000 description 5
• 101800000733 Angiotensin-2 Proteins 0.000 description 5
• 239000004215 Carbon black (E152) Substances 0.000 description 5
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 5
• 101000579218 Homo sapiens Renin Proteins 0.000 description 5
• CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 5
• PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 description 5
• 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 5
• 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 5
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
• 230000002378 acidificating effect Effects 0.000 description 5
• 229950006323 angiotensin ii Drugs 0.000 description 5
• 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 5
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
• 229910000024 caesium carbonate Inorganic materials 0.000 description 5
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
• 229910052802 copper Inorganic materials 0.000 description 5
• 239000010949 copper Substances 0.000 description 5
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 5
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 5
• 229930195733 hydrocarbon Natural products 0.000 description 5
• 238000000338 in vitro Methods 0.000 description 5
• 238000011065 in-situ storage Methods 0.000 description 5
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 5
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 5
• JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 5
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 5
• 238000010534 nucleophilic substitution reaction Methods 0.000 description 5
• 125000004193 piperazinyl group Chemical group 0.000 description 5
• 238000003756 stirring Methods 0.000 description 5
• 239000000126 substance Substances 0.000 description 5
• 239000003981 vehicle Substances 0.000 description 5
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 4
• XYSSNBNFOBVMAU-UHFFFAOYSA-N 2-chloro-1h-indole-3-carbaldehyde Chemical class C1=CC=C2C(C=O)=C(Cl)NC2=C1 XYSSNBNFOBVMAU-UHFFFAOYSA-N 0.000 description 4
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
• 239000005541 ACE inhibitor Substances 0.000 description 4
• 102000004881 Angiotensinogen Human genes 0.000 description 4
• 108090001067 Angiotensinogen Proteins 0.000 description 4
• LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 4
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
• 230000001154 acute effect Effects 0.000 description 4
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
• 150000001412 amines Chemical class 0.000 description 4
• 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 4
• 230000003276 anti-hypertensive effect Effects 0.000 description 4
• 229940054051 antipsychotic indole derivative Drugs 0.000 description 4
• 229910052786 argon Inorganic materials 0.000 description 4
• 230000004872 arterial blood pressure Effects 0.000 description 4
• 230000036772 blood pressure Effects 0.000 description 4
• 150000001718 carbodiimides Chemical class 0.000 description 4
• 150000001768 cations Chemical class 0.000 description 4
• 238000012512 characterization method Methods 0.000 description 4
• 230000008878 coupling Effects 0.000 description 4
• 238000010168 coupling process Methods 0.000 description 4
• 238000005859 coupling reaction Methods 0.000 description 4
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 4
• 125000005842 heteroatom Chemical group 0.000 description 4
• 125000000623 heterocyclic group Chemical group 0.000 description 4
• 238000004128 high performance liquid chromatography Methods 0.000 description 4
• 238000005984 hydrogenation reaction Methods 0.000 description 4
• 230000007062 hydrolysis Effects 0.000 description 4
• 238000006460 hydrolysis reaction Methods 0.000 description 4
• 230000002401 inhibitory effect Effects 0.000 description 4
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
• 239000003960 organic solvent Substances 0.000 description 4
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